Although great progress has been made in the understanding of the genetic and cellular aspects of testis differentiation, little research has been devoted to specifying genetic controls for ovary development. This lack of attention to the subject is due in part to the assumption that ovaries develop passively as the default pathway for gonadal formation whenever testis genes are absent. My proposed research intends to determine whether mammalian ovary development is regulated by the expression of genes and, if so, to characterize how gene expression affects ovary development and function. The cDNA subtraction hybridization that I am conducting allows me to approach various possible genetic pathways to ovary formation. For example, I can address the possibility of ovaries forming because of either gene up- or down-regulation in somatic cells, germ cells, or both. I have so far identified four novel genes with expression patterns and predicted protein products indicative of roles in female sexual differentiation. Candidate genes will be analyzed using cell culture, biochemical analyses, gene knockout and transgenic technologies. The importance of these studies transcend beyond the understanding of how ovaries develop, as they will also contribute to the understanding of female fertility and ovarian cancers. [unreadable] [unreadable]